Skip to main content
SpringerLink
Log in

Role of toll-like receptors in regulatory functions of T and B cells

  • Review
  • Immunology
  • Published:
Chinese Science Bulletin

Abstract

Pathogens can find their ways to most sites in the host. Pathogen sensors, such as Toll-like receptors (TLRs), must be equally and broadly distributed on immune cells to combat them through innate and adaptive immunity. Most classes of TLRs are found in innate immune cells to obtain an immediate response against pathogens, but recent studies indicate that a number of TLRs are wildly expressed in T and B cells, suggesting TLRs also directly regulate adaptive immune responses. Due to the rapid increase of new information on the multiple roles of TLRs, in this paper we aim to review several main properties of TLRs and their direct role in T and B cells. This review consists of 6 parts: (i) Characteristics of Toll-like receptors (TLRs) and signaling; (ii) signalling pathways of TLRs; (iii) TLR expressions on human leukocytes; (iv) TLR expressions and functions in the Th1, CD4+CD45RO+ memory T cells and regulatory/suppressor T as well as B cell populations; (v) therapeutic potential of TLR agonists; (Vi) discussion and perspective. The latest findings and potential therapeutic applications are discussed. There is growing evidence supporting the concept that TLR activation contributes not only to innate immunity but also to adaptive immunity, including direct regulation of both T and B lymphocytes by TLRs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hoebe K, Beutler B. TLRs as bacterial sensors. In: O’Neill L A, Brint E, eds. Toll-like Receptors in Inflammation. Base Boston, Berlin: Birkäuser Verlag, 2006. 1–17

    Google Scholar 

  2. Beutler B. Inferences, questions and possibilities in Toll-like receptor signaling. Nature, 2004, 430: 257–263

    Article  PubMed  CAS  Google Scholar 

  3. Belvin M P, Anderson K V. A conserved signaling pathway: The Drosophila Toll-dorsal pathway. Annu Rev Cell Dev Biol, 1996, 12: 3343–3416

    Article  Google Scholar 

  4. Lemaitre B E, Nicolas L, Michaut J M, et al. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell, 1996, 86: 973–983

    Article  PubMed  CAS  Google Scholar 

  5. Poltorak A, He X L, Simirnova I, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutationos in Tlr4 gene. Science, 1998, 282: 2085–2088

    Article  PubMed  CAS  Google Scholar 

  6. Zarember K A, Godowski P J. Tissue expression of human Toll-like receptors and differential of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, cytokines. J Immunol, 2002, 168: 554–561

    PubMed  CAS  Google Scholar 

  7. McGettrick A F, O’Neill L A. Toll-like receptors: key activators of leukocytes and regulator of haematopoiesis. Brit J Haematology, 2007, 139: 185–193

    Article  CAS  Google Scholar 

  8. Ligoxygakis P, Bulet P, Reichhart J M. Critical evaluation of the role of the toll-like receptor 18-wheeler in the host defense of Drosophila. EMBO Rep, 2002, 3: 666–673

    Article  PubMed  CAS  Google Scholar 

  9. Uematsu S, Akira S. Toll-like receptors and type I interferons. J Biol Chem, 2007, 282: 15319–15323

    Article  PubMed  CAS  Google Scholar 

  10. Akira S. Mammalian Toll-like receptors. Curr, Opin, Immun, 2003, 15: 5–11

    Article  CAS  Google Scholar 

  11. Hayden M S, Ghosh S. NF-kB in the innate immune system. In: Ghosh S, ed. Hand Book of Transcription Factor NF-kappa B. London: CRC Press, Taylor & Francis Group, 2007. 107–129

    Google Scholar 

  12. Shi Y, White D, He L, et al. Toll-like receptor tolerizes malignant B cells and enchances killing by cytotoxic agents. Cancer Res, 2007, 67: 1823–1831

    Article  PubMed  CAS  Google Scholar 

  13. Wang J, Shao Y, Bennett T A, Shankar R A, et al. The functional effects of physical interactions among Toll-like receptors 7, 8, 9. J Biol Chem, 2006, 281: 37427–37434

    Article  PubMed  CAS  Google Scholar 

  14. Gururajan M, Jacob J, Pulendran B. Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets. PLoS ONE, 2007, 2: e863

    Article  PubMed  Google Scholar 

  15. Babu S, Blauvelt C P, Kumaraswami V, et al. Diminished T cell TLR expression and function modulated the immune response in human filarial infection. J Immunol, 2006, 176: 3885–3889

    PubMed  CAS  Google Scholar 

  16. Weaver C T, Hatton R D, Mangan P R, et al. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol, 2007, 25: 821–852

    Article  PubMed  CAS  Google Scholar 

  17. Wei L, Laurance A, Elias K M, et al. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT-dependent manner. J Biol Chem, 2007, 282: 34605–34610

    Article  PubMed  CAS  Google Scholar 

  18. Imanishi T, Hara H, Susuki S, et al. TLR2 directly triggeres Th1 effector functions. J Immunol, 2007, 178: 6715–6719

    PubMed  CAS  Google Scholar 

  19. Peng G, Guo Z, Kiniwa Y, et al. Toll-like receptor 8 mediated-reversal of CD4+ regulatory T cell function. Science, 2005, 309: 1380–1384

    Article  PubMed  CAS  Google Scholar 

  20. Jonuleit H, Schmitt E. The regulatory T cell family: distinct subsets and their interrelations. J Immunol, 2003, 171: 6323–6327

    PubMed  CAS  Google Scholar 

  21. Caramalho I, Lopes-Carvalho T, Ostler D, et al. Regulatory T cells selectively express Toll-like receptors and are activated by Lipopolysaccharide. J Exp Med, 2003, 197: 403–411

    Article  PubMed  CAS  Google Scholar 

  22. Crellin N K, Garcia R V, Hadisfar O, et al. Human CD4+ T cell expressivemTLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells. J Immunol, 2005, 175: 8051–8059

    PubMed  CAS  Google Scholar 

  23. Bell M P, Svingen P A, Rahman M K, et al. FOXP3 regulates TLR10 expression in human T regulatory cells. J Immunol, 2007, 179: 1893–1900

    PubMed  CAS  Google Scholar 

  24. Xu D, Komai-Koma M, Liew F Y. Expression and function of Toll-like receptor on T cells. Cell Immu, 2005, 233: 85–89

    Article  CAS  Google Scholar 

  25. Bernasconi N, Nobuyuki O, Lanzavecchia A. A role for Toll-like receptors in acquired immunity: Up-regulation of TLR9 by BCR triggering in naïve B cells and constitutive expression in memory B cells. Blood, 2003, 101: 4500–4504

    Article  PubMed  CAS  Google Scholar 

  26. Leonard J P, Link B K, Emmanouilides C, et al. Phase I trial of Toll-like receptor 9 agonist PF-3512676 with and following Rituximab in patients with recurrent indolent and aggressive non-Hodgkin’s lymphoma. Clin Cancer Res, 2007, 13: 6168–6174

    Article  PubMed  CAS  Google Scholar 

  27. Wysocka M, Benoit B M, Newton S, et al. Enhancement of the host immune responses in cutaneous T-cell lymphoma by CpG oligodeoxynucleoides and IL-15. Blood, 2004, 104: 4142–4149

    Article  PubMed  CAS  Google Scholar 

  28. Wille-Reece U, Flynn B J, Loré K, et al. Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. J Exp Med, 2006, 203: 1249–1258

    Article  PubMed  CAS  Google Scholar 

  29. Wille-Reece U, Flynn B J, Loré K, et al. HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc Natl Acad Sci USA, 2005, 102: 15190–15194

    Article  PubMed  CAS  Google Scholar 

  30. Janway C A Jr, Travers P, Walpot M, et al. Adaptive immunity to infection. In: Janeway C, Travers P, Walport M, eds. Immunobiology: The Immune System in Health and Disease. 6th ed. London: Garland Publishers, Taylor & Francis Group, 2005. 409–459

    Google Scholar 

  31. Spaner D E, Masellis A. Toll-like receptor agonists in the treatment of chronic lymphocytic leukemia. Leukemiam 2007, 21: 53–60

    Article  CAS  Google Scholar 

  32. Janway C A Jr, Travers P, Walpot M, et al. Manipulation of the immune response. n: Janeway C, Travers P, Walport M, eds. Immunobiology: The Immune System in Health and Disease. 6th ed. London: Garland Publishers, Taylor & Francis Group, 2005. 613–662

    Google Scholar 

  33. Han J H, Akira S, Calame K, et al. Class swith recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptor. Immunity, 2007, 27: 64–75

    Article  PubMed  CAS  Google Scholar 

  34. Li C, Wang Y, Gao L, et al. Expression of toll-like receptor2 and 4 and CD14 during differentiation of HL-60 cells induced by phorbol 12-myristant 13-acetate and 1α, 25-dihydroxy-vitamin D3. Cell Growth Differ, 2002, 13: 27–38

    PubMed  Google Scholar 

  35. Celis E. Toll-like receptor ligands energize peptide vaccines through multiple paths. Cancer Res, 2007, 67: 7945–7947

    Article  PubMed  CAS  Google Scholar 

  36. Kawakami Y, Fujita T, Kudo C, et al. Dendritic cell based personalized immunotherapybased on cancer antigen research. Front Biosci, 2008, 13: 1952–1958

    Article  PubMed  CAS  Google Scholar 

  37. Roses R E, Xu M, Koski G K, et al. Radiation therapy and Toll-like receptor signaling: Implications for the treatment of cancer. Oncogene, 2008, 27: 200–207

    Article  PubMed  CAS  Google Scholar 

  38. Huleatt J W, Nakaar V, Desai P, et al. Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine, 2008, 26: 201–214

    Article  PubMed  CAS  Google Scholar 

  39. Iqbal S M, Kaul R. Mucosal innate immunity as a determinat of HIV susceptibility. Am J Repr Immunol, 2008, 59: 44–54

    CAS  Google Scholar 

  40. Goldman M. Translational mini-review series on Toll-like receptors: Toll-like receptor ligands as novel pharmaceuticals for allergic disorders. Clin Exp Immun, 2007, 147: 208–216

    PubMed  CAS  Google Scholar 

  41. Kanzler H, Barrat F J, Hessel E M, et al. Therapeutic targeting of innate immunity with Toll-like receptor agonists and antogonists. Nat Med, 2007, 13: 552–559

    Article  PubMed  CAS  Google Scholar 

  42. Goriely S, Goldman M. From tolerance to antoimmunity: Is there a risk in early life vaccination? J Comp Path, 2007, 137: S57–S61

    Article  PubMed  CAS  Google Scholar 

  43. Whiteside T L. Immune suppression in cancer: Effect on immune cells, mechanisms and future therapeutic intervention. Semin Cancer Biol, 2006, 16: 3–15

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China

    ZongLiang Chang

Authors
  1. ZongLiang Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to ZongLiang Chang.

About this article

Cite this article

Chang, Z. Role of toll-like receptors in regulatory functions of T and B cells. Chin. Sci. Bull. 53, 1121–1127 (2008). https://doi.org/10.1007/s11434-008-0184-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11434-008-0184-x

Keywords

Search

Navigation